miR-378-mediated glycolytic metabolism enriches the Pax7^(Hi) subpopulation of satellite cells  

作　　者：Hu Li Lin Kang Rimao Wu Changyin Li Qianying Zhang Ran Zhong Lijing Jia Dahai Zhu Yong Zhang 

机构地区：[1]The Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine,Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou 510005,China [2]The State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and School of Basic Medicine,Peking Union Medical College,Beijing 100005,China [3]Department of Endocrinology,the Second Clinical Medical College of Jinan University,Shenzhen People’s Hospital,Shenzhen 518020,China

出　　处：《Cell Regeneration》2022年第1期109-118,共10页细胞再生（英文）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(91949106,31971080 and 32000603);the Natural Science Foundation of Beijing(7192125).

摘　　要：Adult skeletal muscle stem cells,also known satellite cells(SCs),are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma.Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration.Herein,we demonstrate that microRNA 378(miR-378)regulates glycolytic metabolism in skeletal muscle fibers,as evidenced by analysis of myofiber-specific miR-378 transgenic mice(TG).Subsequently,we evaluate SC function and muscle regeneration using miR-378 TG mice.We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs.Furthermore,we show that the miR-378-mediated metabolic switch enriches Pax7^(Hi) SCs,accounting for impaired muscle regeneration in miR-378 TG mice.Mechanistically,our data suggest that miR-378 targets the Akt1/FoxO1 pathway,which contributes the enrichment of Pax7^(Hi) SCs in miR-378 TG mice.Together,our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.

关 键 词：satellite cells muscle regeneration MIRNAS glycolytic metabolism 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]